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Special Announcement About Tolvaptan
November 3, 2012
At the American Society of Nephrology Annual Meeting and in a simultaneous
publication in the New England Journal of Medicine, a group of investigators led by Dr.
Vicente Torres from the Mayo Clinic reported the results of the Tolvaptan Efficacy and
Safety in Management of Autosomal Dominant Polycystic Kidney Disease Outcomes
(TEMPO) Trial. Tolvaptan, a drug developed by Otsuka Pharmaceuticals, blocks the
binding of the hormone vasopressin to its receptor in the kidney. Vasopressin causes
production of the molecule cyclic Adenosine MonoPhosphate (cAMP) in the kidney.
cAMP is thought to accelerate the progression of Autosomal Dominant Polycystic
Kidney Disease (ADPKD) by stimulating fluid secretion into cysts and stimulating
proliferation of cells lining cyst cavities. Thus it was hoped that tolvaptan, which should
decrease kidney production of cAMP, would slow progression of ADPKD.
In the TEMPO Trial, over 1,400 ADPKD patients worldwide were randomly assigned to
receive a placebo (sugar pill) or tolvaptan and followed for 3 years. Each of them was
periodically assessed for total kidney volume (as assessed by MRI), kidney function, and
selected other clinical outcomes. Tolvaptan slowed the growth of polycystic kidneys,
decreased clinically significant kidney pain, and slowed deterioration of kidney function.
Patients who received Tolvaptan had more side effects related to increased urine
production and liver test abnormalities; patients who received placebo had more adverse
effects due to ADPKD-related issues.
Though tolvaptan is already approved for treatment of other medical conditions, the
doses of tolvaptan used in the TEMPO trial were significantly higher than used in
previous studies of other diseases. In addition, ADPKD patients are a unique patient
population. Thus, until the data are reviewed in detail by Otsuka and by the FDA, it
could be dangerous to take tolvaptan for treatment of PKD.
Nonetheless, this is an exciting milestone for ADPKD patients and the PKD Foundation.
This is the first time that a drug specifically targeted to alter ADPKD progression in
humans has been shown to be of benefit. The concept of using vasopressin blockade as
a way of slowing ADPKD progression was originally developed by Dr. Vincent Gattone,
whose research has been in part supported by the PKD Foundation.
Frequently Asked Questions
Will tolvaptan be approved by the FDA for treatment of PKD?
If Otsuka asks for approval from the FDA (and comparable regulatory agencies outside
the United States) for the use of tolvaptan to treat ADPKD, the FDA will review in depth
all the data presented by Otsuka (primarily the data from the TEMPO trial) to assess the
relative risks and benefits of using tolvaptan in this way. If Otsuka submits an
application in this regard, we do not yet know whether the FDA will approve tolvaptan
for treatment of ADPKD.
What are the side effects of tolvaptan?
Based on previous studies of tolvaptan for treatment of other diseases, individuals taking
tolvaptan would be expected to experience thirst and to urinate frequently. Patients who
received Tolvaptan in the TEMPO Trial had more side effects related to increased urine
production and liver test abnormalities; patients who received placebo had more adverse
effects due to ADPKD-related issues. Whether there will be other side effects that were
manifest in the TEMPO trial will be revealed as Otsuka and the FDA review the TEMPO
data in detail.
Can my Doctor prescribe tolvaptan?
Tolvaptan is already approved for treatment of other medical conditions, but has not been
evaluated by the FDA or other regulatory agencies for use in ADPKD. It is important to
realize that the doses of tolvaptan used in the TEMPO trial were significantly higher than
those used in previous studies of other diseases. In addition, ADPKD patients are a
unique patient population and doctors who take care of patients with ADPKD have little
or no experience in using this medication for outpatients. Thus, until the data are
reviewed in detail by Otsuka and by the FDA, it could be dangerous to take tolvaptan for
treatment of ADPKD. In addition, insurance companies will mostly likely not pay for
tolvaptan for treatment of ADPKD unless it is approved by the FDA for this condition,
and as currently available, tolvaptan is very expensive.
Can anybody with PKD take tolvaptan?
The TEMPO trial studied only adult patients with Autosomal Dominant PKD. Whether
tolvaptan will be of benefit for patients with other types of PKD is unknown.